[Prevention of aspergillosis with itraconazole in neutropenic patients: importance of drug monitoring]

Bull Acad Natl Med. 1999;183(2):371-80; discussion 380-1.
[Article in French]

Abstract

Itraconazole is being used increasingly as prophylaxis of systemic aspergillosis in patients with immunodepression. Therapeutic itraconazole monitoring by plasma concentrations measurement is justified by its dose-dependent pharmacokinetics, drug interactions, and frequent bioavailability modifications observed in immunocompromised patients. A first study was carried out in 16 patients with haematological malignancies, given chemotherapy plus itraconazole 400-800 mg/day in a single dose as prophylactic treatment. Therapeutic through drug plasma concentration (Cmin > or = 250 ng/ml of itraconazole, or > or = 750 ng/ml of itraconazole plus hydroxyitraconazole) was not reached in 5/16 patients. Moreover results emphasised the wide inter and intra-individual variability of the steady-state plasma concentrations. In another study we used a multiple dose regimen (100-200 mg x 3/day), instead of a single dose regimen. An adequate Cmin value was found in 34/36 patients. In conclusion, the wide inter and intra-individual variability of itraconazole pharmacokinetics necessitate regularly to measure the drug plasma concentrations in patients with life-threatening fungal infections.

Publication types

  • English Abstract

MeSH terms

  • Antifungal Agents / blood
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / blood
  • Aspergillosis / drug therapy*
  • Case-Control Studies
  • Drug Monitoring / methods*
  • Humans
  • Itraconazole / blood
  • Itraconazole / therapeutic use*
  • Neutropenia / microbiology*

Substances

  • Antifungal Agents
  • Itraconazole